Oral cancer causes significant mortality and morbidity, with only approximately 50% of patients surviving beyond 5 years. Among the survivors, surgical resections, radiation and chemotherapies cause long term functional impairment and sharp drops in quality of life. The genetic predisposition of humans to develop oral premalignancies and invasive oral epithelial cancer is not adequately understood. The Oral Cancer Genetics Consortium (OCGC), a consortium of investigators from the NIH, Harvard University, University of Chicago, New York University and MD Anderson Cancer Center proposes to conduct the first-ever whole genome scan of oral cancer to identify loci of significant cancer susceptibility and to study gene environment interactions. The focus of this application is initial genotyping and discovery. While a replication set is not included in this application, OCGC includes scientists eligible for a future replication study on a multi-racial group of oral cancer patients. A case control study design is proposed, involving the genotyping of already collected human DNA samples from patients with invasive oral cancer, oral premalignancies and normal controls. Our initial analysis will examine the association between 2,500,000 (genotyped and imputed) SNPs and oral cancer phenotypes. Approximately 550,000 SNPs will be directly genotyped using the Illumina Human Hap 550K Bead chip;the remaining will be imputed using dense genotyping data from the HapMap and the computationally efficient Hidden Markov Model in MACH.